Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Temporal Arteritis I’ll be talking to you today about temporal arteritis. In terms of history, Ali Eban Isa was a first century oculist, actually the premier oculist in Bagdad. He was the first to write about this entity. He described it as heat and inflammation of the temporal muscles which sometimes ended in loss of vision. Hutchinson gave the first English report of inflamed and swollen temporal arteries in 1980. Horton, who you see pictured here, was really the first to define the clinical characteristics of giant cell arteritis, or temporal arteritis, and it is still known by the eponym of Horton’s disease. Jennings later reported the first case of blindness and Ginonni first described the pillow sign; that is peoples’ temples are so tender that they cannot rest their head on the pillow. He is also the first to advocate steroid treatment for this disease. The prevalence of this disease ranges from 10 to 15 cases per hundred thousand population in the United States. There is a female predominance. They are four to six times more at risk. This disease rarely occurs in patients younger than 50 years of age. The mean age of onset is about 70 years old and there is a high incidence in all patients older than 80 years of age, about 1%. In terms of racial breakdown, it is more frequent in white patients of Northern European descent. This is a study done out of UCLA where they looked at 126 temporal artery biopsies over the past years. They found that out of 66 white patients, 19 were positive, giving them a 29% positive rate. Out of the nine Asian patients biopsied only one was positive, giving 11%. Very interestingly, out of the 40 Hispanic patients biopsied, none of them came back positive, which is consistent with what we found in our case presentation, and 0 out of 11 African-American patients had positive biopsies. Given this data, it is not surprising that this disease is more frequent in Scandinavia and Olmstead County, Minnesota. There is a very well established overlap of polymyalgia rheumatica. These are closely rated conditions in a spectrum of disease. There are 50 to 90% of patients with temporal arteritis who have polymyalgia rheumatica and vice versa about 20 to 33% of patients with polymyalgia rheumatica have temporal arteritis by biopsy. Now polymyalgia rheumatica presents with pain and stiffness in the neck, shoulders and hips. They also have constitutional symptoms such as fatigue, weight loss and a low-grade fever, which are some of the constitutional symptoms you see with temporal arteritis as well. The exact relationship of these two entities is unclear. Going to anatomy, this disease most often strikes the cranial arteries, in particular the superficial temporal artery. It is the terminal branch of the external carotid. The temporal artery, for our purposes, lies in the danger zone for the frontal branch of the facial nerve. As you can see here, that is certainly one of the biggest complications of biopsy. You can see here, this is a cross section of the temporal region. The temporal artery lies in the temporoparietal fascia and the frontal branch of the facial nerve lies just on the undersurface, so this is definitely in danger during biopsy of this artery. This disease strikes the medium and large arteries of the head and neck. These arteries are infiltrated by the cellular arm of the immune system, and again, the superficial temporal artery is the one that is most often hit. The visual symptoms come from attack on the posterior ciliary and ophthalmic arteries. It is also notable that the cellular changes may extend into the carotids and aorta and there has also been an association of thoracic aneurysms with this disease. Here is a schematic of a blood cell. You can see the endothelium and the intima. This is the area that gets attacked by temporal arteritis, as well as atherosclerosis. The media is a smooth muscle layer bounded by the internal elastic lamina and external elastic lamina. There is also an outer adventitia. We will go over a histologic slide shortly. One theory is that there is a foreign body giant cell attack on the calcified internal elastic membrane in already atherosclerotic arteries. This attack causes a chronic inflammation, which leads to vessel dilation and very extensive intimal thickening. Up here you see a picture of a normal blood vessel. You see the very thin intimal layer, the smooth muscle layer and the adventitial layer. Here is an artery attacked by temporal arteritis. You can see here a very thickened and inflamed intimal layer, a smooth medial layer and the adventitia here. Looking a little closer at the actual lesion in the intima you can see that there is a T-cell recruitment and activation. The CD-4 cells are activated in the adventitia and they move into the intima and produce T-cell cytokines, which propagate the inflammatory cascade. Here is a picture of activated macrophages. As you can see they often form multinucleated giant cells in the intima. These monocytes also secrete metalloproteinases and produce free radicals, which also propagate the inflammatory cascade. This eventually leads to lumen obstructive intimal hyperplasia as you can see here. You can see necrosis of the arterial wall with granulomatous disruption of the elastic lamina and in situ thrombosis, although giant cells, which are present here are not necessary for your diagnosis. Now there is a genetic predisposition that they found to temporal arteritis; it is related to HLA type. It has also been linked to polymorphisms of ICAM-1 and interleukin-1 receptor antagonist. There have been some theories that put forth that infection is a trigger mechanism for this disease. There have been sudden onset cases that all happen in one place that suggested an environmental cause. Outbreaks have been noted in Scandinavia and Olmstead County. Some of the etiologic agents that have been put forth include influenza, hepatitis B, parvovirus, Chlamydia, and mycoplasma. Now the American College of Rheumatology has put forth a set of diagnostic criteria which state that if you have three out of five of the following criteria, you have temporal arteritis: Age greater than 50 at disease onset, a new headache, temporal artery tenderness or decreased pulse, an ESR greater than 50 mm/hour, and an abnormal temporal artery biopsy. If three of these five criteria are met there is a sensitivity of 93% and specificity of 91%. The differential diagnosis of this disease includes tension headache or migraine, dental disease, trigeminal neuralgia, sinus or otologic disease. That is a big reason why knowledge of this disease is important to our specialty and, of course, cerebrovascular disease. Here is how these patients present. Thirty-two percent of patients will present with headache. This disease is also diagnosed when polymyalgia rheumatica is already a known entity. The will also, a small percent, present with fever, visual symptoms, weakness, and tenderness over the artery. After the disease is already diagnosed, upon later questioning these patients will complain of weight loss and anorexia, jaw claudication, loss of vision and decreased temporal artery pulse, and we will go over these symptoms in more detail. Headache is a universal symptom often reported in as many as 95% of cases. It tends to be a unilateral headache and a burning or jabbing sensation on the scalp or the face. It is often worse at night and, again, the pillow sign is very sensitive resting your head on your temple exacerbates the pain. Often these patients cannot wear a hat or glasses because of the pain. Jaw claudication is also a known symptom. It is very prominent when the patient is chewing or talking, and occurs in approximately 65% of patients. Constitutional symptoms are nonspecific, but they are often there and they include a low-grade fever, night sweats, anorexia and weight loss, malaise, fatigue and depression. Now visual loss may present as the first symptom and this is the reason that we need to maintain a high degree of suspicion for this disease. About 50% of patients with this disease complain of impaired vision and that could be either transient visual blurring, diplopia, pain in the eye or sudden loss of vision. The onset may occur suddenly and painlessly and it certainly may mimic cerebrovascular accident. Loss may be transient, the amaurosis fugax or permanent. Permanent blindness eventually occurs in 20 to 50% of untreated cases, so it is very important to recognize this disease. The blindness occurs from inflammation in the ophthalmic and the posterior ciliary arteries, which supply the optic nerve. As it turns out, if a patient is anemic and has a low ESR, it is associated with less risk of visual loss. Bilateral visual loss is also a possibility and the second eye is usually affected in some way within two to three weeks of the first. This disease strikes medium to large size arteries throughout the entire body and so you have a very large spectrum of symptoms that are possible. They include facial swelling, tongue infarction has been reported, respiratory problems, cardiovascular disease, gastrointestinal disease, and neurological disease which includes all sorts of syndromes, including peripheral neuropathy, brain stem and spinal cord involvement. Now in terms of physical exam these patients will usually present to you with a low-grade fever, perhaps mild meningeal signs. They will generally have exquisite tenderness of the temporal region, warmth of the temporal region and pulselessness. Sometimes you can roll the thickened and dilated artery between your fingers and the patient’s skull. Sometimes they will also have tender and necrotic scalp nodules, which you see here. On ophthalmologic exam they will often exhibit abnormal visual acuity and visual fields, due to ophthalmologic nerve involvement. Diplopia is also a common symptom, either because of cranial nerve VI palsy, which you see in a picture here. She has a left-sided cranial nerve VI palsy. Ischemic myopathy of the ocular motility muscles are also a possibility, as well as brain stem ischemia. Pupillary abnormalities are also seen with temporal arteritis as well. On funduscopic inspection, the fundus may appear entirely normal, however, you can also often see a pale edematous optic disc. This is the result of optic neuropathy and is actually an ophthalmologic emergency. These patients need to be admitted and placed on steroids immediately. You can also see scattered cotton-wool patches and small flame hemorrhaged and distended, beaded retinal veins. Now, in terms of laboratory studies, the essential study that you need to order is erythrocyte sedimentation rate. This is a general test of inflammation. It was developed by Alf Westergren, who first developed the test, this is in 1918. He developed the test to determine the prognosis of patients with tuberculosis. In the Westergren method, you take a tube about 200 mm high and 2.5 mm in diameter and you fill the column with anticoagulated blood. The distance that the column of blood falls in one hour is reported in millimeters per hour. As you can see, when there are increased inflammatory proteins in the blood it causes the blood cells to settle slower causing a higher number. A normal ESR is one-half the patient’s age generally; you add ten if the patient is female. With temporal arteritis the ESR is usually greater than 80 mm an hour. However, in about 5 to 10% of biopsy-proven cases the ESR is less than 30 mm an hour. ESR is useful in that it tells you disease activity and also guides the length of time that you give treatment. Other laboratory studies that may be abnormal are C-reactive protein, it may be elevated in some patients and is especially useful if there is a normal ESR. CBC can often show leukocytosis, mild anemia or thrombocytosis. As it happens, almost one-half of the patients with temporal arteritis test abnormal in their liver function tests. The gold standard for diagnosis of this disease and the reason why these patients are generally sent to our clinic is a temporal artery biopsy. This has a sensitivity anywhere from 60-80%. There are some pitfalls, however. If a unilateral superficial temporal artery biopsy is negative, biopsy on the other side is really not that helpful. There is only a 3 to 5% positive rate. You should also note that after these patients have started the steroid therapy that the diagnostic yield is diminished. However, this should not delay therapy because they are certainly at risk for visual loss without being treated. In terms of the technique of the biopsy it is pretty straight forward. You should biopsy the specific area of tenderness. If there is no specific area of tenderness you should biopsy at least a 3 to 5 cm segment. Often times because this disease shows characteristic skip lesions; there can be areas of normal artery interposed between areas of affected artery. As we said before, the facial nerve is at risk. This unfortunately is a histologic section of a superficial temporal artery but right along side of it is a biopsy of the patient’s frontal branch of the facial nerve. To avoid this complication, you should avoid deep dissection past the artery. Ultrasound is another way to diagnose this disease. There have been several studies recently that have promoted colored duplex ultrasonography to diagnose temporal arteritis. You can often see stenosis, as you can see here, complete occlusion of the artery, and you can also see a halo around the artery, which represents arterial edema from the inflammation. There has been reported a 73% sensitivity and 100% specificity, however, you certainly would need an ultrasonographer who was skilled in reading these. Other modalities to diagnose the disease include MRI and MRA. With temporal arteritis you often see patchier diffuse dural enhancement, which you can see here, optic nerve enhancement, and there can sometimes be a multi-infarct state secondary to arteritis of the cranial arteries. Angiography is not very useful, but if you do an angiogram on this patient you can sometimes see occlusion or alternating stenotic areas. A PET scan has also been studied in terms of this disease and you can see some uptake in the arteries consistent with arteritis. Now, in terms of treatment, corticosteroids are the mainstay of treatment. Patients suspected to have this disease should really begin therapy immediately with steroids. It precludes the need to wait for blood work or a temporal artery biopsy to start the steroids; prednisone about 40 to 60 mg a day. If they are complaining of visual symptoms you should give them a much higher dose. Some ophthalmologists advocate admitting these patients and placing them on IV steroids. There is a possibility for visual improvement when the steroids are started and they also would prevent further visual loss or second eye involvement, which often can happen within two to three weeks of the first eye. The response to steroids should be dramatic, within 48 to 72 hours, and you should continue the full dose until either the symptoms are completely resolved or the ESR returns to normal; usually in about two to four weeks. You should taper the steroids very slowly, no more than 10% every two weeks because these patients are often high-risk for relapse. You should also monitor them closely as an outpatient for clinical relapse or an elevated ESR. Some people advocate alendronate therapy to prevent osteoporosis because often these patients are older patients and they are often on these steroids for up to a year. Combined therapy with prednisone and methotrexate has been studied. They have shown a decreased relapse rate from 84% to 45% in a double blind study. In steroid-resistant cases you can place these patients on cyclosporin and azathioprine or cyclosporin and methotrexate, but you would certainly want to warn them about the possible side effects from that therapy. Complications of temporal arteritis can be profound. They include visual loss like we had talked about before. If a patient has temporal arteritis and is unrecognized they can have permanent blindness in about 20 to 50% of the case. Cerebral stroke is the most common cause of death in patients with temporal arteritis. If this disease goes unchecked they can develop amyloidosis, which can often lead to nephrotic syndrome and end-stage renal disease. Interestingly, hearing loss has also been reported in about 20 cases, and the theory is that they develop vertebrobasilar terminal cochleovestibular arteritis. This hearing loss is sudden, bilateral and steroid-responsive. This disease is a self-limited disease. It can last for as long as several months to as long as five years. However, the relapse rate can be as high as 25%. If a patient is going to relapse, the most likely time is going to be in the first 18 months of therapy or within 12 months of cessation of treatment. Again, these patients are often on steroid therapy for as long as a year. There really is no way to predict which patients are at risk for relapse. Future areas of study include ways to try to stop the inflammatory cascade. These could include suppression of T-cell activity, suppression of cytokines, as well as anti-interferon gamma. Suppression of tissue digestion by the metalloproteinases secreted by the macrophages and antioxidants which would fight the free radicals produced by the macrophages as well. So, in summary, temporal arteritis is a systemic vasculopathy affecting the cranial vessels of older patients. You should really hold a high index of suspicion for this disease because there is an up to 50% incidence of blindness in untreated cases. Steroid therapy should be started immediately. Temporal artery biopsy is a gold standard for diagnosis. You should biopsy a long segment to address any skip lesions, and unilateral biopsies are usually sufficient. Case presentation: H.T. is a 59-year old Hispanic female referred to the BTGH ENT clinic from her primary care doctor with a 6-month history of temporal headaches, low grade fever, and jaw claudication. She denied any visual changes or loss of vision. She also denied joint pain. Her medical history was remarkable for brittle IDDM, which precluded steroid therapy until a definitive diagnosis was obtained. On physical exam, she was a well nourished female in no apparent distress. Ears: TMs intact without effusion. Nose: no lesions, no drainage. OC/OP: no lesions, tongue midline, palate symmetric. Neck: no LAD or bruits. Head: bilateral temporal tenderness, no sinus tenderness. Eyes: EOMI, PERRL, visual fields intact. Laboratory studies included a normal complete blood count and an ESR of 60. A temporal artery biopsy was obtained. Bibliograhpy: Altlparmak MR, Tabak F, Pamuk ON, Pamuk GE, Mert A, Aktuglu Y. Giant cell arteritis and secondary amyloidosis: the natural history. Scand J Rheumatol 2001;30:114-116. Atalay MK, Bluemke DA. Magnetic resonance imaging of large vessel vasculitis. Curr Opin Rheumatol 2001;13:41-47. Bhatti MT, Goldstein MH. Facial nerve injury following superficial temporal artery biopsy. Dermatol Surg 2001;27:15-17. Gonzalez-Gay MA. Genetic epidemiology: Giant cell arteritis and polymyalgia rheumatica. Arthritis Res 2001;3:154-157. Gonzalez-Gay MA, Garcia-Porrua C, Llorca J, Hajeer AH, Branas F, Dababneh A, Gonza Louzao C, Rodriguez-Gil E, Rodriguez-Ledo P, Ollier WE. Visual manifestations of giant cell arteritis: Trends and clinical spectrum in 161 patients. Medicine 2000;79:283-292. Horton BT, Magath TB, Brown, GE. An undescribed form of arteritis of the temporal vessels. Proc Staff Meet Mayo Clin 1932;7:100-101. Hunder GG. Temporal arteritis and polymyalgia rheumatica. In : Kelley WN, et al. Textbook of Rheumatology . 4th ed. Philadelphia: Saunders, 1993:103-12. Hutchinson J. Diseases of the arteries. On a peculiar form of thrombotic arteritis of the aged which is sometimes productive of gangrene. Arch Surg ( London) 1890;1:323-329. Joelson E, Ruthrauff B, Ali F, Lindeman N, Sharp FR. Multifocal dural enhancement associated with temporal arteritis. Arch Neurol 2000;57:119-122. Jover JA, Hernandez-Garcia C, Morado IC, Vargas E, Banares A, Fernandez-Gutierrez B. Combined treatment of giant-cell arteritis with methotrexate and prednisone. a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2001;134:106-114. Liu NH, LaBree LD, Feldon SE, Rao NA. The epidemiology of giant cell arteritis: A 12-year retrospective study. Ophthalmol 2001;108:1145-1149. Pless M, Rizzo JF 3rd, Lamkin JC. Concordance of bilateral temporal artery biopsy in giant cell arteritis. J Neuroophthalmol 2000;20:216-218. Salvarani C, Hunder GG. Giant cell arteritis with low erythrocyte sedimentation rate: frequency of occurrence in a population-based study. Arthritis Rheum 2001;45:140-145. Saadoun D, Cacoub P, Costedoat-Chalumeau N, Sbai A, Piette JC. Horton's disease and corticosteroid-responsive hearing loss. Ann Med Interne (Paris) 2000;151:600-602. Schmidt WA . Doppler ultrasonography in the diagnosis of giant cell arteritis. Clin Exp Rheumatol 2000;(4 Suppl 20):S40-S42. Schmidt WA, Kraft HE, Vorpahl K, Volker L, Gromnica-Ihle EJ. Color duplex ultrasonography in the diagnosis of temporal arteritis. N Engl J Med 1997;337:1336-1342. Stanson AW. (2000) Imaging findings in extracranial (giant cell) temporal arteritis. Clin Exp Rheumatol 2000;18(4 Suppl 20):S43-S48. Turlakow A, Yeung HW, Pui J, Macapinlac H, Liebovitz E, Rusch V, Goy A, Larson SM. Fludeoxyglucose positron emission tomography in the diagnosis of giant cell arteritis. Arch Intern Med 2001;161:1003-1007. Grand Rounds Archive | Department Home page BCM Public | BCM Intranet | Privacy Notices | Contact BCM | BCM Site Map | ©2001-2005 Baylor College of Medicine
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